rs638416

Variant names:

• chr17-18363661-G-A
• rs638416
• NM_004169.5:c.-309C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-18363661-G-A
• chr17-18363661-G-C
• chr17-18363661-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004169.5(SHMT1):​c.-309C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 35)
• Consequence: SHMT1 NM_004169.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.02
• Publications: 11 publications found

Genes affected

SHMT1 (HGNC:10850): (serine hydroxymethyltransferase 1) This gene encodes the cytosolic form of serine hydroxymethyltransferase, a pyridoxal phosphate-containing enzyme that catalyzes the reversible conversion of serine and tetrahydrofolate to glycine and 5,10-methylene tetrahydrofolate. This reaction provides one-carbon units for synthesis of methionine, thymidylate, and purines in the cytoplasm. This gene is located within the Smith-Magenis syndrome region on chromosome 17. A pseudogene of this gene is located on the short arm of chromosome 1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004169.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHMT1	NM_004169.5	MANE Select	c.-309C>T		upstream_gene	N/A	NP_004160.3
	SHMT1	NM_148918.3		c.-309C>T		upstream_gene	N/A	NP_683718.1	P34896-2
	SHMT1	NM_001281786.2		c.-607C>T		upstream_gene	N/A	NP_001268715.1	P34896-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHMT1	ENST00000316694.8	TSL:1 MANE Select	c.-309C>T		upstream_gene	N/A	ENSP00000318868.3	P34896-1
	SHMT1	ENST00000583780.2	TSL:1	c.-448C>T		upstream_gene	N/A	ENSP00000462041.2	P34896-1
	SHMT1	ENST00000354098.7	TSL:1	c.-309C>T		upstream_gene	N/A	ENSP00000318805.3	P34896-2

Frequencies

GnomAD3 genomes Cov.: 35

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.18
DANN	Benign	0.94
PhyloP100		-4.0
PromoterAI		-0.12	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs638416; hg19: chr17-18266975;